Molecular Characterization of HLA-B27 in Anterior Uveitis: Integrated Serological and Genetic Analysis Reveals Elevated Antigen Levels and Variants Concentrated in Exons 2 and 3

Shinta Stri Ayuda Nur Setyaningsih (School of Life Sciences and Technology, Institut Teknologi Bandung, Jl. Ganesa 10, Lebak Siliwangi, Coblong, Bandung 40135)
Arief Akhdestira Mustaram (National Eye Center, Cicendo National Eye Hospital, Jl. Cicendo 4, Babakan Ciamis, Sumur Bandung, Bandung 40117)
Angga Fajriansyah (National Eye Center, Cicendo National Eye Hospital, Jl. Cicendo 4, Babakan Ciamis, Sumur Bandung, Bandung 40117)
Patriotika Muslima (National Eye Center, Cicendo National Eye Hospital, Jl. Cicendo 4, Babakan Ciamis, Sumur Bandung, Bandung 40117)
Elfa Ali Idrus (National Eye Center, Cicendo National Eye Hospital, Jl. Cicendo 4, Babakan Ciamis, Sumur Bandung, Bandung 40117)
Muhammad Hamzah Syaifullah Azmi (School of Life Sciences and Technology, Institut Teknologi Bandung, Jl. Ganesa 10, Lebak Siliwangi, Coblong, Bandung 40135)
Elsa Gustianty (National Eye Center, Cicendo National Eye Hospital, Jl. Cicendo 4, Babakan Ciamis, Sumur Bandung, Bandung 40117)
Ernawati Arifin Giri-Rachman (School of Life Sciences and Technology, Institut Teknologi Bandung, Jl. Ganesa 10, Lebak Siliwangi, Coblong, Bandung 40135)
Marselina Irasonia Tan (School of Life Sciences and Technology, Institut Teknologi Bandung, Jl. Ganesa 10, Lebak Siliwangi, Coblong, Bandung 40135)

The Indonesian Biomedical Journal
Vol 18, No 3 (2026)

BACKGROUND: Anterior uveitis is the most common form of intraocular inflammation and an important cause of visual morbidity worldwide. Human leukocyte antigen B27 (HLA-B27) is a well-established immunogenetic risk factor; however, its molecular diversity remains insufficiently characterized in Indonesian populations. This study was conducted to characterize HLA-B27 at both the serological and genetic levels by quantifying serum antigen levels and identifying sequence variations in the HLA-B27 gene associated with anterior uveitis in Indonesian patients.METHODS: Thirteen anterior uveitis patients who were clinically evaluated through the Standardization of Uveitis Nomenclature (SUN) criteria were involved in this study. Blood sample was collected from subjects, and serum HLA-B27 concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Genomic DNA was analyzed using combined Sanger and Oxford Nanopore sequencing. Variant calling and annotation were performed using a custom bioinformatics pipeline.RESULTS: Serum HLA-B27 antigen levels were significantly higher in anterior uveitis patients than in healthy reference controls. Sequence analysis identified 43 patient-exclusive variants after exclusion of shared polymorphic changes, from which 13 recurrent or potentially functionally relevant variants were prioritized for downstream analysis. These variants were predominantly distributed within exons 2 and 3 and comprised single-nucleotide substitutions, coding-region insertion–deletion events, and one promoter-region insertion. Several coding variants resulted in amino acid substitutions, while adjacent compensatory indel pairs were also identified among exon 2 frameshift-associated variants.CONCLUSION: Anterior uveitis is associated with both elevated circulating HLA-B27 antigen levels and sequence variation within functionally important regions of the HLA-B27 gene, particularly exons 2 and 3. The identified missense substitutions, coding-region indels, and promoter insertion suggest potential effects on peptide binding, molecular stability, immune interaction, intracellular protein handling, or transcriptional regulation.KEYWORDS: anterior uveitis, HLA-B27, genomic variants, peptide-binding groove, protein misfolding